Influence of ranibizumab treatment on the extracellular matrix in patients with neovascular age-related macular degeneration

Med Sci Monit. 2014 May 28:20:875-83. doi: 10.12659/MSM.890031.

Abstract

Background: We know the influence of the intravitreal anti-vascular endothelial growth factor (VEGF) injections on the choroidal neovascularization in the course of exudative age-related macular degeneration (AMD). However, the influence of the ranibizumab therapy in question on the extracellular matrix (ECM) remains unknown. We aimed to estimate the influence of Lucentis intravitreal injections on the gene expression of structural components of the extracellular matrix in patients with neovascular AMD.

Material and methods: Patients with subfoveal localization of neovascularization in AMD, which was clinically active and observed using optical coherence tomography, were treated with ranibizumab (0.5 mg/0.05 mL) in accordance with the PrONTO scheme. Total RNA was extracted from peripheral blood mononuclear cells, and an oligonucleotide microarray technique enabled comparison of the expression level of genes encoding collagens, elastin, and laminins in AMD patients compared to control subjects.

Results: After 3 intravitreal injections of ranibizumab (Lucentis), COL1A1 and COL6A1 genes showed increased expression, whereas decreased expression mainly occurred for the following genes: COL4A5, COL11A1, OL4A6C, LAMB4, and LAMC2.

Conclusions: Anti-VEGF local therapy influences the gene expression of structural components of the ECM as measured from blood samples. The loading dose of ranibizumab for the retina changes the expression of collagen and laminin genes, but does not influence the expression of the elastin gene.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Case-Control Studies
  • Choroidal Neovascularization / drug therapy*
  • Choroidal Neovascularization / pathology*
  • Collagen / genetics
  • Collagen / metabolism
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism*
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Intravitreal Injections
  • Laminin / genetics
  • Laminin / metabolism
  • Macular Degeneration / drug therapy*
  • Macular Degeneration / pathology*
  • Male
  • Ranibizumab

Substances

  • Antibodies, Monoclonal, Humanized
  • Laminin
  • Collagen
  • Ranibizumab